A novel NHERF1 mutation in human breast cancer inactivates inhibition by NHERF1 protein in EGFR signaling

Du, G., Hao, C., Gu, Y., Wang, Z., Jiang, Wen Guo ORCID: https://orcid.org/0000-0002-3283-1111, He, J. and Cheng, S. 2016. A novel NHERF1 mutation in human breast cancer inactivates inhibition by NHERF1 protein in EGFR signaling. Anticancer Research 36 (3) , pp. 1165-1174.

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Abstract

Background: Na+/H+ exchanger regulatory factor 1 (NHERF1) has been reported to interact with many cancer-related proteins. We recently identified a novel NHERF1 mutation (E43G) in breast tumours. Materials and Methods: The candidates of NHERF1 mutation were identified in breast cancer tissues by polymerase chain reaction and DNA sequencing. Wild-type NHERF1 and E43G mutation were expressed in NHERF1-knockdown cells (MCF7ΔNHERF1) and low-NHERF1-expressing cells (SKMES-1). The effects of mutated NHERF1 on cell functions were examined using in vitro methods. Glutathione S-transferase pull-down assays and western blotting were performed to study the effects of NHERF1 mutation on its interaction with cancer-related proteins. Results: Compared to wild-type NHERF1, expression of the mutated NHERF1 failed to suppress malignant traits in cancer cells, attenuated interaction of NHERF1 protein with epidermal growth factor receptor (EGFR), and inactivated its inhibition of EGF-induced Akt and extracellular regulated protein kinases (ERK) activation. Conclusion: The results show the causal role of NHERF1 in the regulation of the EGFR pathway and the progression of breast cancer.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Publisher:	International Institute of Anticancer Research
ISSN:	0250-7005
Funders:	Cardiff China Medical Scholarship, Cancer Research Wales
Date of First Compliant Deposit:	9 April 2016
Date of Acceptance:	14 February 2016
Last Modified:	16 Nov 2024 16:15
URI:	https://orca.cardiff.ac.uk/id/eprint/89024

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